1. Field of the Invention
The present invention relates to probes, assays and kits for diagnosing infertility in men.
2. Description of the Prior Art
In the medical study and practice of human reproduction, infertility is usually defined as the inability to conceive after 1 year of trying. The term infertility is not the same as sterility, since many couples ultimately may achieve a pregnancy after 1 year of unprotected intercourse. Over 4.5 million American men and women—or roughly 1 out of 5 (15-20%) couples—fail when attempting their first pregnancy. In these couples, about half of the men will have a significant abnormality that makes them unable to father children. Male infertility may be caused by abnormalities in the testes or other areas of the male reproductive tract, as well as immune system defects. Yet the most common cause of male infertility is disordered sperm production. Other medical conditions that could cause infertility include a varicocele, abnormalities of the testes, penis, prostate or secondary sex traits.
Four main factors govern male fertility: hormones, sperm production, the ductal system of sperm delivery, and sexual function. Among these factors, physical variables that affect the structure of the testes are particularly important. There are many types of male infertility with a variety of causes and results.
“Varicocele” describes dilated internal spermatic veins forming the pampiniform plexus. This dilation results from increased intra-abdominal and hydrostatic pressures transmitted to the internal spermatic veins. Varicoceles have been associated with a common type of male infertility in which there is loss of ipsilateral testicular volume, oligozoospermia with increased numbers of sperm with a tapered head shape (“stress pattern”), impaired sperm motility and a reduced ability to undergo an acrosome reaction.
Approximately 40% of males from infertile couples present with varicocele. The mechanism(s) underlying the production of infertility with varicocele, however, are poorly characterized. The most widely accepted explanation for the pathophysiology of varicocele in male infertility is abnormally elevated testicular temperature due to impaired heat transfer by the scrotum and/or changes in testicular blood flow. Although men with varicocele exhibit higher mean scrotal temperatures, there is a large overlap with the range of scrotal temperatures in fertile men. More importantly, only 13% of men with varicocele are infertile, and, although varicocele repair has been documented to reduce testicular temperature, only ⅓ of infertile men with varicocele-associated infertility will experience a return of fecundity following varicocele correction. These findings suggest that varicocele may not be a primary cause of infertility and that it is the interaction of varicocele with other factors that produces the infertile state.
Other etiologies of human male infertility include such conditions as cryptorchidism, retrograde ejaculation, testicular tumor, endocrine disorders, Kallmann's syndrome, fertile eunuch syndrome, congenital adrenal hyperplasia, Prader-Willi syndrome, Lawrence-Moon-Biedl syndrome, hemochromatosis, primary hypogonadism, Klinefelter's syndrome, XX disorder, XYY syndrome, mixed gonadal dysgenesis, Noonan syndrome, Myotonic dystrophy, 5-alpha-reductase deficiency, androgen receptor deficiency, among other known conditions.